Ethicists have raised concerns that elderly patients with a progressively debilitating disease such as Parkinson's disease (PD) may be too vulnerable for research that involves novel, invasive interventions (such as gene transfer and cell transplants) that use a controversial masking design, i.e., sham neurosurgical controls. A common ethical concern is that the subjects' desire for therapeutic benefit may compromise the quality of their decisions. Are these subjects laboring under a therapeutic misconception (TM), a phenomenon in which subjects conflate research with individualized treatment, or some related phenomena, e.g., seriously misestimating the risks and benefits of research participation? There is an increasing number of PD clinical trials proposing the sham control design, so this important ethical issue will continue to arise. This project proposes to study enrollees and decliners of four actual PD neurosurgical clinical trials that involve a sham surgery control. Because there is no standard method for assessing TM and indeed because it remains a controversial and evolving issue, this project's main aim is to describe in depth from the subjects' perspective their decision whether to participate in such studies. A semi-structured interview method (Conditional Probe Interview) has been developed to provide an in depth account of the subjects' motivations, expectations, understanding, and decision-making process-emphasizing the subjects' rationale for each and the relationship between them. We will conduct a combination of prospective and retrospective interviews; those subjects who decline after screening interviews will also be interviewed. Enrollees of the trials will also be followed longitudinally, so any changes in motivations, attitudes, or understanding can be assessed. A unique focus of this project is that the analysis will emphasize the entirety of the subject's narrative as the context for analyzing specific statements that may or may not indicate TM related phenomena. Thus, the subject becomes the primary unit of analysis in the interpretation of individual statements. A complementary qualitative and quantitative analytic approach will be used. By providing an in depth, context-sensitive account of how seriously ill neurological patients make participation decisions regarding research involving sham neurosurgery controls, this project will (1) provide invaluable insights for optimizing informed consent practices for future sham surgery controlled trials; and (2) clarify the key controversial aspects, and the complex contours of, TM and related phenomena. PUBLIC HEALTH RELEVANCE: This project addresses the ethical challenges of human subject research when subjects with serious illnesses are enrolled in clinical trials involving sham surgery controls. In particular, it will enhance the mission of NINDS by focusing on the ethics of sham surgery controls in Parkinson's disease neurosurgical trials-a design that is increasingly used in testing novel surgical interventions for PD. Specifically, the results of this study will provide important insights into how to minimize or even eliminate serious misconceptions or misunderstandings on the part of participants that may compromise the quality of their consent.